DISCOVERIES (ISSN 2359-7232), 2017, July-September issue

CITATION: 

Submitted: Sept. 3rd, 2017; Revised: Sept. 27th, 2017; Accepted: Sept. 29th, 2017; Published: Sept. 30, 2017;

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Strains of Pathological Protein Aggregates in Neurodegenerative Diseases

Xinzhu Wang (1,2), Zeinab Noroozian (1,3), Madelaine Lynch (1,3), Nicholas Armstrong (1), Raphael Schneider (1,2,4), Mingzhe Liu (1,3), Farinaz Ghodrati (1,2), Ashley B. Zhang (1,2), Yoo Jeong Yang (5), Amanda C. Hall (1), Michael Solarski (1,2), Samuel A. Killackey (1), Joel C. Watts (2,6,*) 

(1) Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

(2) Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada

(3) Sunnybrook Research Institute - Biological Sciences, Toronto, ON, Canada

(4) Department of Medicine, Division of Neurology, University of Toronto, Toronto, ON, Canada

(5) Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada

(6) Department of Biochemistry, University of Toronto, Toronto, ON, Canada

*Corresponding author: Joel C. Watts, PhD, Tanz Centre for Research in Neurodegenerative Diseases and Department of Biochemistry, University of Toronto, Krembil Discovery Tower, Rm. 4KD481, 60 Leonard Ave., Toronto, ON, Canada, M5T 2S8;  

Abstract

The presence of protein aggregates in the brain is a hallmark of neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Considerable evidence has revealed that the pathological protein aggregates in many neurodegenerative diseases are able to self-propagate, which may enable pathology to spread from cell-to-cell within the brain. This property is reminiscent of what occurs in prion diseases such as Creutzfeldt-Jakob disease. A widely recognized feature of prion disorders is the existence of distinct strains of prions, which are thought to represent unique protein aggregate structures. A number of recent studies have pointed to the existence of strains of protein aggregates in other, more common neurodegenerative illnesses such as AD, PD, and related disorders. In this review, we outline the pathobiology of prion strains and discuss how the concept of protein aggregate strains may help to explain the heterogeneity inherent to many human neurodegenerative disorders.

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